Acquired immunodeficiency syndrome (AIDS) is a disease which is the ultimate result of infection with human immunodeficiency virus (HIV). Currently, there is no effective vaccine which can protect the human population from HIV infection and hence the development of an efficacious HIV-vaccine and protocol for administering the same is urgently required. Previously, HIV-1 particles exhaustively inactivated by chemical treatments, a vaccinia vector encoding the whole envelope protein (gp160) of HIV-1, and purified recombinant gp120 have been evaluated as candidate HIV vaccines. Although inactivated HIV-1 virus preparations elicited a T-cell-mediated Delayed-Type Hypersensitivity (DTH) reaction in humans, and vaccinia/gp160 and gp120 recombinant vaccine candidates induced virus neutralizing antibodies, none of these immunogens have been shown to be efficacious human HIV vaccines. The inventors' interest in HIV vaccinology is to develop synthetic HIV-1 peptide vaccines and consider that their use alone or in conjunction with other HIV-1 vaccine candidates may lead to the elicitation of more effective immune responses against HIV-1.
The inventors' had previously described in their granted U.S. Pat. No. 5,817,318 (European Patent No. 470,980) and U.S. Pat. No. 5,639,854, the disclosures of which are incorporated herein by reference, inter alia, the identification and characterization of a T-cell epitope of the core protein, p24E, of HIV-1, and its usage in the construction of immunogenic synthetic chimeric peptides comprising p24E linked to amino acid sequences of different B-cell epitopes of an envelope or core protein of HIV-1.
The present effort has turned to the design of HIV vaccines capable of eliciting cell-mediated immunity (CMI) and protocols for the use thereof. In this context, the inventors have focused interest on a viral protein, Rev, expressed early during the life cycle of the HIV-virus, for the reason that the carboxyl terminal half is rich in human cytotoxic T-cell (CTL) motifs. Peptides which are generated via immunization with an appropriately constructed vaccine containing the Rev protein, therefore, may be presented in the context of the Major Histocompatibility Complex (MHC) class 1 molecules to induce CTL effector responses capable of killing virus infected cells early to limit virus spread. However, the immunization protocol provided herein is applicable to T-cell epitope containing peptides derived from other HIV proteins.